This work was supported in part by a grant from the Federal Government and the Government therefore has certain rights in the invention.
This invention relates to recombinant LCF, DNA, and uses thereof.
CD4, a cell-cell adhesion protein, is expressed on a subset of T lymphocytes (Krensky et al., Proc. Natl. Acad. Sci. USA 79: 2365-2369, 1982; Biddison et al., J. Exp. Med. 156: 1065-1076, 1982; and Wilde et al., J. Immunol. 131: 152-157, 1983), mononuclear cells (Stewart et al., J. Immunol. 136: 3773-3778, 1986), and eosinophils (Rand et al., J. Exp. Med. 173: 1521-1528, 1991). In lymphocytes, CD4 contributes to antigen receptor signaling (Collins et al., J. Immunol. 148: 2159-2162, 1992; Anderson et al., J. Immunol. 139-678-682, 1987; Eichmann et al., J. Immunol. 17: 643-650, 1987; Walker et al., Eur. J. Immunol. 17: 873-880 1987; and Sleckman et al., Nature 328: 351-353, 1987) by direct interaction with MHC Class II molecules (Doyle et al., Nature 330: 256-259, 1987). In addition, a natural soluble lymphokine, lymphocyte chemoattractant factor (LCF), requires cell surface expression of CD4 to induce chemotactic activity in monocytes (Cruikshank et al., J. Exp. Med. 173: 1521-1528, 1991) and T lymphocytes (Cruikshank et al., J. Immunol. 138: 3817-3823, 1987; Cruikshank et al., J. Immunol. 146: 2928-2934, 1991). In concert with its chemoattractant activity LCF acts as a competence growth factor for human T lymphocytes (Cruikshank et al., J. Immunol. 138: 3817-3823, 1987).
LCF is a cationic, 56-kD glycoprotein representing the tetrameric form of four 14-kD monomeric chains. LCF is produced by T lymphocytes and is specifically chemoattractant for CD4+ T-cells, monocytes and eosinophils (see, e.g., Berman et al. Cell Immunol. 95: 105-112, 1985; Rand et al., JEM 173: 1521-1528, 1991). Secretion of LCF by CD8+ T cells occurs (Cruikshank et al., J. Immunol. 138: 3817, 1987;) after stimulation by mitogen, antigen, histamine or serotonin. The latter two are of particular interest because degranulated mast cells and basophils are present in tissue sites of delayed-type hypersensitivity reactions (see, e.g., Askenase Prog. Allergy 23: 199-320, 1977). Induction of LCF by a mast cell or a basophil product provides a link between the early mediator phase of the immune response and the development of the later T-lymphocyte-predominant inflammatory reaction.